PROJECT SUMMARY This proposed project addresses FOA: NIH RFA-FD-19-024: Conduct studies to establish more targeted durations of use for certain approved antimicrobial new animal drugs in food animals. Optimizing antimicrobial usages and promoting judicious antimicrobial use are pivotal to preserving the efficacy of medically-important antimicrobials and vital to protecting food security. The long-term goal of this work is to promote sustainable livestock production through judicious antimicrobial use to control active infection of the hemoparasitic pathogen, Anaplasma marginale (Am), the etiologic agent of bovine anaplasmosis. Chlortetracycline (CTC) antimicrobials are the only FDA-approved drug to control anaplasmosis and may currently be administered continuously during the entire pasture-feeding season and beyond if under an active VFD. Continuous exposure to a single drug class for prolonged periods introduces strong selective pressure for the development of resistance. The guiding hypothesis of this proposal is that targeting antimicrobial treatment to coincide with strategic periods in the Am transmission cycle will effectively control active anaplasmosis and minimize risk of antimicrobial resistance. Through integrated cooperation between scientists and clinicians, the hypothesis will be tested, using the current FDA-approved CTC labeled dose indicated for the control of active anaplasmosis, by answering the following questions: (i) Is the current FDA- approved dosage of CTC effective to control active anaplasmosis? (ii) In what timeframe, relative to infection, must CTC treatment be initiated (targeted) to effectively control active anaplasmosis? (iii) For what duration must CTC treatment be administered to effectively control active anaplasmosis? (iv) Can a strategic interval CTC treatment protocol, derived from the above information, effectively control active anaplasmosis long-term?, and (v) Is this CTC treatment protocol broadly effective against diverse Am strains? Data generated from this proposal will provide pivotal evidence for the effectiveness of CTC, at the current FDA-approved label dose, when administered within an appropriately-timed target treatment window and for a defined treatment duration. Together, the goal of this proposal is to provide pivotal data to drug sponsors, federal policy makers, and veterinarians on an effective targeted and defined duration of use CTC treatment protocol, at the current FDA-approved label dose, to control active anaplasmosis in cattle, while also protecting antimicrobial efficacy through promoting judicious antimicrobial use.